The overall goal of this project is to use state-of-the-art anatomic and functional imaging methods to evaluate evidence directed towards understanding the pathophysiology of Attention Deficit Hyperactivity Disorder (ADHD), a complex, heterogeneous disorder that is in need of specification at the neurologic level. Hypotheses about neural mechanisms have recently focused on deficient response inhibition as one of the features fundamental to the pathophysiology of ADHD; however, the nature of these deficits and their neurologic underpinnings remain unclear. Previous investigators have theorized that the neural mechanisms underlying response inhibition could be localized to a specific frontal/subcortical region, which, once recognized, could then be regarded as the brain basis for ADHD. Recent data from electrophysiology and imaging studies, however, support a multiple-domain model of response inhibition according to which the specific frontal-subcortical circuit crucial for response inhibition depends on the nature of the task being performed: skeletomotor, oculomotor, cognitive, socioemotional. In ADHD, there is evidence for impairment on tasks reflecting all four of these domains of response inhibition; furthermore, recent imaging findings suggest that frontal abnormalities in ADHD involve regions within both premotor and prefrontal cortices. Accordingly, we propose to investigate the hypothesis that deficient response inhibition associated with ADHD is not attributable to abnormality within one specific frontal/subcortical region. Rather, impairments referable to skeletomotor, oculomotor, cognitive, and socioemotional domains of response inhibition are each linked to abnormality within the corresponding frontal-subcortical circuit - skeletomotor, oculomotor, dorsolateral prefrontal and orbitofrontal, respectively. Anatomic MRI and functional MRI will be used to determine which frontal-subcortical circuits are affected in ADHD and at what level; furthermore, which anatomic component abnormalities are associated with which behavioral/cognitive deficits that define ADHD. The findings will advance our understanding of the neuropathophysiology of ADHD, and in doing so provide a foundation for diagnostic models based on neuroanatomic subtypes that go beyond that of symptomatic presentation; this can lead to an improved framework for understanding the genetic and neurochemical basis of ADHD and for examining therapies targeted at specific fundamental deficits associated with ADHD. [unreadable] [unreadable]